Previous studies have demonstrated that the age-related changes in the collagen network correlate with the increased fragility of aged bone. However, the underlying mechanism is still not well understood. The overall goal of this study is to explore the underlying mechanism of age-related changes in the collagen network of bone, and their role in the increased fragility of aged bone. First of all, we seek to answer two research questions: 1) whether age-related changes in the collagen network are induced by bone remodeling process, and 2) whether such changes directly contribute to the age-related decrease in the toughness of bone. In this study, we hypothesize that age-related changes in collagen may be induced by the bone remodeling process, and such changes may lead to the weakening of the collagen network, and consequently cause a decreased toughness of aged bone. To test these hypotheses, we propose to address the following three specific aims: Aim 1: To determine age-related changes in the collagen network in both secondary osteons and interstitial bone regions - Hypothesis: The integrity of collagen molecules (i.e., extent of collagen denaturation and crosslinks) in secondary osteons changes with age, whereas the interstitial bone matrix does not experience these changes. Aim 2: To determine age-related changes in the mechanical integrity of bone tissues in both secondary osteons and interstitial bone regions - Hypothesis: The mechanical integrity of secondary osteons changes with age, whereas the interstitial bone matrix does not experience these change. Aim 3: To determine if age-related changes in the collagen network are correlated with the decrease in the toughness of bone (as a tissue) with aging - Hypothesis: Age-related changes in the collagen network weaken the mechanical integrity of bone and consequently lead to the observed decrease in the toughness of bone with aging This study will furnish the insight information on the underlying mechanisms of age-related deterioration in bone quality and will facilitate future studies in the prevention and treatment of age and disease-related bone fractures.